Arl13b in primary cilia regulates the migration and placement of interneurons in the developing cerebral cortex

Dev Cell. 2012 Nov 13;23(5):925-38. doi: 10.1016/j.devcel.2012.09.019.

Abstract

Coordinated migration and placement of interneurons and projection neurons lead to functional connectivity in the cerebral cortex; defective neuronal migration and the resultant connectivity changes underlie the cognitive defects in a spectrum of neurological disorders. Here we show that primary cilia play a guiding role in the migration and placement of postmitotic interneurons in the developing cerebral cortex and that this process requires the ciliary protein, Arl13b. Through live imaging of interneuronal cilia, we show that migrating interneurons display highly dynamic primary cilia and we correlate cilia dynamics with the interneuron's migratory state. We demonstrate that the guidance cue receptors essential for interneuronal migration localize to interneuronal primary cilia, but their concentration and dynamics are altered in the absence of Arl13b. Expression of Arl13b variants known to cause Joubert syndrome induce defective interneuronal migration, suggesting that defects in cilia-dependent interneuron migration may in part underlie the neurological defects in Joubert syndrome patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / deficiency
  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / physiology*
  • Abnormalities, Multiple
  • Animals
  • Cell Movement / physiology
  • Cerebellar Diseases / etiology
  • Cerebellar Diseases / pathology
  • Cerebellar Diseases / physiopathology
  • Cerebellum / abnormalities
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology
  • Cerebral Cortex / growth & development*
  • Cerebral Cortex / physiology*
  • Cilia / physiology*
  • Eye Abnormalities / etiology
  • Eye Abnormalities / pathology
  • Eye Abnormalities / physiopathology
  • Humans
  • Interneurons / physiology*
  • Kidney Diseases, Cystic / etiology
  • Kidney Diseases, Cystic / pathology
  • Kidney Diseases, Cystic / physiopathology
  • Mice
  • Mice, Transgenic
  • Mutant Proteins / genetics
  • Mutant Proteins / physiology
  • Retina / abnormalities
  • Retina / pathology
  • Retina / physiopathology

Substances

  • Arl13b protein, mouse
  • Mutant Proteins
  • ADP-Ribosylation Factors
  • Arl13b protein, human

Supplementary concepts

  • Agenesis of Cerebellar Vermis